Trauma is the leading cause of death in the United States in persons under the age of 40. Those who survive initial shock and trauma may subsequently die of sequential multiple organ failure. Specific abnormalities that contribute to this sequential organ failure and mortality are (1) progressive pulmonary insufficiency, (2) refractory head injury, (3) systemic sepsis, and (4) impaired host defense mechanisms due to deficient opsonic protein and reticulo-endothelial function. An interdisciplinary team of surgeons, physiologists, biomedical engineers, biochemists and mathematicians has undertaken to apply sophisticated and quantitative techniques to the study of the pathophysiology of severely injured patients. The unique nature of this interaction enhances the rapid expansion of basic research observations into the clinical situation for verification and application. This will lead to novel therapeutic techniques which should prevent sequential organ failure and improve survival of trauma patients. The therapeutic modalities include: (a) correction of disordered ventilation-perfusion imbalance, (b) identification and correction of increased capillary permeability, (c) identification and treatment of hypoxia due to respiratory failure following head trauma, (d) reversal of opsonic protein deficiency by infusion of plasma cryoprecipitate, thereby reversing the RE dysfunction, (e) prevention of renal failure by mannitol and cryoprecipitate therapy, and (f) prevention of sequential multiple organ failure. Achievement of these aims will be facilitated by the development of biomedical instrumentation technology and automated processes for data acquisition and analysis.